• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1727-1735
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• 2012

Regardless of advances in treatment modalities with the invention of newer therapies, breast cancer remains a major health problem with respect to its diagnosis, treatment and management. This female malignancy with its tremendous heterogeneous nature is linked to high incidence and mortality rates, especially in developing region of the world. It is the malignancy composed of distinct biological subtypes with diverse clinical, pathological, molecular and genetic features as well as different therapeutic responsiveness and outcomes. This inconsistency can be partially overcome by finding novel molecular markers with biological significance. In recent years, newer technologies help us to indentify distinct biomarkers and increase our understanding of the molecular basis of breast cancer. However, certain issues need to be resolved that limit the application of gene expression profiling to current clinical practice. Despite the complex nature of gene expression patterns of cDNAs in microarrays, there are some innovative regulatory molecules and functional pathways that allow us to predict breast cancer behavior in the clinic and provide new targets for breast cancer treatment. This review describes the landscape of different molecular markers with particular spotlight on vitamin D signaling pathway and apoptotic specific protein of p53 (ASPP) family members in breast cancer.

• Molecules and Cells
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• 제41권10호
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• pp.909-916
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• 2018

In pancreatic ${\beta}$ cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3'-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in ${\beta}$ cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in ${\beta}$ cells. PTBP1 is present in ${\beta}$ cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized ${\beta}$ cells established from wild-type (${\beta}IRWT$) mice are higher than levels in ${\beta}$ cells established from IR-null (${\beta}IRKO$) mice, and ectopic re-expression of IR-WT in ${\beta}IRKO$ cells restored PTBP1 levels. However, PTBP1 levels were not altered in ${\beta}IRKO$ cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in ${\beta}IRWT$ cells, but not in ${\beta}IRKO$ cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic ${\beta}$ cells.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.520-528
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• 2021

Plesiomonas shigelloides, a member of the family Vibrionaceae, is a gram-negative, rod-shaped, facultative anaerobic bacterium with flagella. P. shigelloides has been isolated from such sources as freshwater, surface water, and many wild and domestic animals. P. shigelloides contains 102 O-antigens and 51 H-antigens. The diversity of O-antigen gene clusters is relatively poorly understood. In addition to O1 and O17 reported by other laboratories, and the 12 O serogroups (O2, O10, O12, O23, O25, O26, O32, O33, O34, O66, O75, and O76) reported previously by us, in the present study, nine new P. shigelloides serogroups (O8, O17, O18, O37, O38, O39, O44, O45, and O61) were sequenced and annotated. The genes for the O-antigens of these nine groups are clustered together in the chromosome between rep and aqpZ. Only O38 possesses the wzm and wzt genes for the synthesis and translocation of O-antigens via the ATP-binding cassette (ABC) transporter pathway; the other eight use the Wzx/Wzy pathway. Phylogenetic analysis using wzx and wzy showed that both genes are diversified. Among the nine new P. shigelloides serogroups, eight use wzx/wzy genes as targets. In addition, we developed an O-antigen-specific PCR assay to detect these nine distinct serogroups with no cross reactions among them.

• Animal cells and systems
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• 제1권3호
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• pp.515-520
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• 1997

Male accessory glands and ejaculatory duct of Drosophila melanogaster are reproductive organs which synthesize secretory seminal proteins. Several products of these organs involved in egg laying, receptivity, and sperm stability or storage were isolated from their lumens. Despite their secretory process play an important role, exocytosis pathway in these organs is not well known. In the present study, we characterized secretory protein profiles and determined their secretory mechanisms. Eight accessory gland secretory proteins and two ejaculatory duct secretory proteins were detected in their lumens. All these proteins were constitutively synthesized in these organs and secreted to their lumens. Secretion of newly synthesized proteins initiated at about 1 h after synthesis, and reached the peak at 4 h after synthesis. It seems that secretion of the proteins may occur via constitutive exocytosis pathway.

• Molecules and Cells
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• 제27권6호
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• pp.657-665
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• 2009

The ovomucoid pre-mRNA has been folded into mini-hairpins adaptable for the RNA recognition motif (RRM) protein binding. The number of mini-hairpins were 372 for pre-mRNA and 83-86 for mature mRNA. The spatial arrangements are, in average, 16 nucleotides per mini-hairpin which includes 7 nt in the stem, 5.6 nt in the loop and 3.7 nt in the inter-hairpin spacer. The constitutive splicing system of ovomucoid-pre-mRNA is characterized by preferred order of intron removal of 5/6 > 7/4 > 2/1 > 3. The 5' splice sites (5'SS), branch point sequences (BPS) and 3' splice sites (3'SS) were identified and free energies involved have been estimated in 7 splice sites. Thermodynamic barriers for splice sites from the least (|lowest| -Kcal) were 5, 4, 7, 6, 2, 1, and 3; i.e., -18.7 Kcal, -20.2 Kcal, -21.0 Kcal, -24.0 Kcal, - 25.4 Kcal, -26.4 Kcal and -28.2 Kcal respectively. These are parallel to the kinetic data of splicing order reported in the literature. As a result, the preferred order of intron removals can be described by a consideration of free energy changes involved in the spliceosomal assembly pathway. This finding is consistent with the validity of hnRNP formation mechanisms in previous reports.

• BMB Reports
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• 제40권6호
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• pp.966-972
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• 2007

Pituitary tumor transforming gene (PTTG1) is widely detected in many tumors. Increasing evidence reveals that PTTG1 is associated with cell proliferation, cellular transformation and apoptosis. However, the functions of PTTG1, especially its role in DNA damage-induced apoptosis, remain largely unclear. In this report, we used UV irradiation to induce apoptosis in HeLa cells to examine the role of PTTG1 in UV-induced apoptosis by RNAi-mediated knockdown and overexpression of PTTG1. RNAi-mediated knockdown of PTTG1 expression increased and overexpression of PTTG1 decreased the UV-induced apoptosis. Furthermore, UV irradiation decreased PTTG1 mRNA and protein expression. These effects were found to be mediated by JNK pathway. Therefore, PTTG1 had an important anti-apoptotic role in UV-induced apoptosis and this role was mediated by JNK pathway. These results may provide important information for understanding the exact role and the regulation mechanism of PTTG1 in UV-induced apoptosis.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권4호
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• pp.219-226
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• 2000

The application of recombinant DNA technology to restructure metabolic net-work can change metabolite and protein products by altering the biosynthetic pathways in an organism. Although some success has been achieved, a more detailed and thorough investigation of this approach is certainly warranted since it is clear that such methods hold great potential based on the encouraging results obtained so far. In last decade, there have been tremendous advances in the field of glycobiology and the stage has been set for the biotechnological production of glycoproteins for therapeutic use. Today glycoproteins are one of the most important groups of pharmaceutical products. In this study the attempt was made to focus on identifying technologies that may have general application for modifying glycosylation pathway of the yeast cells in order to produce glycoproteins of therapeutic use. The carbohydrates of therapeutic recombinant glycoproteins play very important roles in determining their pharmacokinetic properties. A number of biological interactions and biological functions mediated by glycans are also being targeted for therapeutic manipulation in vivo. For a commercially viable production of therapeutic glycoproteins a metabolic engineering of a host cell is yet to be established.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.497-502
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• 2014

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

• BMB Reports
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• 제56권2호
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• pp.126-131
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• 2023

The abnormal accumulation and aggregation of the misfolded α-synuclein protein is the neuropathological hallmark of all α-synucleinopathies, including Parkinson's disease. The secreted proteins known as netrins (netrin-1, netrin-3, and netrin-4) are related to laminin and have a role in the molecular pathway for axon guidance and cell survival. Interestingly, only netrin-1 is significantly expressed in the substantia nigra (SN) of healthy adult brains and its expression inversely correlates with that of α-synuclein, which prompted us to look into the role of α-synuclein and netrin-1 molecular interaction in the future of dopaminergic neurons. Here, we showed that netrin-1 and α-synuclein directly interacted in pre-formed fibrils (PFFs) generation test, real time binding assay, and co-immunoprecipitation with neurotoxin treated cell lysates. Netrin-1 deficiency appeared to activate the dopaminergic neuronal cell death signal pathway via α-synuclein aggregation and hyperphosphorylation of α-synuclein S129. Taken together, netrin-1 can be a promising therapeutic molecule in Parkinson's disease.

• 한국발생생물학회지:발생과생식
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• 제17권4호
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• pp.389-397
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• 2013

FGF9/16/20 signaling pathway specify the developmental fates of notochord, mesenchyme, and neural cells in ascidian embryos. Although a conserved Ras/MEK/Erk/Ets pathway is known to be involved in this signaling, the detailed mechanisms of regulation of FGF signaling pathway have remained largely elusive. In this study, we have isolated Hr-Erf, an ascidian orthologue of vertebrate Erf, to elucidate interactions of transcription factors involved in FGF signaling of the ascidian embryo. The Hr-Erf cDNA encompassed 3110 nucleotides including sequence encoded a predicted polypeptide of 760 amino acids. The polypeptide had the Ets DNA-binding domain in its N-terminal region. In adult animals, Hr-Erf mRNA was predominantly detected in muscle, and at lower levels in ganglion, gills, gonad, hepatopancreas, and stomach by quantitative real-time PCR (QPCR) method. During embryogenesis, Hr-Erf mRNA was detected from eggs to early developmental stage embryos, whereas the transcript levels were decreased after neurula stage. Similar to the QPCR results, maternal transcripts of Hr-Erf was detected in the fertilized eggs by whole-mount in situ hybridization. Maternal mRNA of Hr-Erf was gradually lost from the neurula stage. Zygotic expression of Hr-Erf started in most blastomeres at the 8-cell stage. At gastrula stage, Hr-Erf was specifically expressed in the precursor cells of brain and mesenchyme. When MEK inhibitor was treated, embryos resulted in loss of Hr-Erf expression in mesenchyme cells, and in excess of Hr-Erf in a-line neural cells. These results suggest that zygotic Hr-Erf products are involved in specification of mesenchyme and neural cells.